The overall goal of this project is to study the biochemical factors that regulate anticancer therapy-induced pulmonary injury. Bleomycin hydrolase is a poorly characterized aminopeptidase B- like enzyme that is a major biochemical determinant in bleomycin-induced pulmonary fibrosis. The pulmonary endothelium appears to maintain high levels of this enzyme activity in some species and this may have an important functional role in preventing lung injury. The specific aims of the proposed research are to: (a) purify and characterize bleomycin hydrolase and other arginine N-terminal exopeptidases, (b) develop monoclonal antibodies directed toward bleomycin hydrolase, (c) study the extent of antigenic homology among the known aminopeptidase B enzymes, (d) measure the content of bleomycin hydrolase in pulmonary and other tissues of various animal species and strains, and (e) determine the relationship between tissue content and activity of bleomycin hydrolase in these animal models to their susceptibility to bleomycin-induced fibrosis.